AIDS is a complex disease with many manifestations that are amenable to molecular and biomarker imaging. A major focus has been on CNS manifestations in patients with dementia or depression, including metabolic abnormalities, alterations in serotonergic markers, and alterations in the mitochondrial translocator protein (TSPO), a marker for inflammation and tissue injury. For example, regional serotonin transporter binding is higher in depressed HIV+ patients compared to non-depressed HIV+ patients. HAART therapy has greatly benefited AIDS patients to the extent that HIV viral loads and CD4 counts can be maintained at acceptable levels for many years. Nonetheless, these patients suffer from a complex spectrum immune system and endothelium problems, including clotting disorders, altered lipid metabolism, and immune senescence. A pro-inflammatory state results, leading to multiple organ manifestations. For example, the risk of death and disability in HAART-controlled HIV patients from cardiovascular problems is similar to that in HIV- patients who are 30 years older. Thus, the problem focus in many HIV patients is shifting to amelioration of the effects of immune senescence and the development of new therapeutic targets. In parallel, new molecular imaging opportunities have arisen, which will be discussed. Molecular imaging in HIV infection continues to be a compelling area of investigation, with increasing opportunities for new drug development and target imaging.